Human
muscle undergoes constant changes. After about age 50, muscle mass
decreases at an annual rate of 1–2 %. Muscle strength
declines by 1.5 % between ages 50 and 60 and by
3 % thereafter. The reasons for these changes include denervation
of motor
units and a net conversion of fast type II muscle fibers
into slow type I fibers with resulting loss in muscle power necessary
for activities of daily living. In addition, lipids are
deposited in the muscle, but these changes do not usually lead to
a loss in body weight. Once muscle mass in elderly subjects
falls below 2 standard deviations of the mean of a young control
cohort and the gait speed falls below 0.8 m/s, a
clinical diagnosis of sarcopenia can be reached. Assessment of muscle
strength
using tests such as the short physical performance battery
test, the timed get-up-and-go test, or the stair climb power test
may also be helpful in establishing the diagnosis. Serum
markers may be useful when sarcopenia presence is suspected and may
prompt further investigations. Indeed, sarcopenia is one of
the four main reasons for loss of muscle mass. On average, it
is estimated that 5–13 % of elderly people aged
60–70 years are affected by sarcopenia. The numbers increase to
11–50 % for
those aged 80 or above. Sarcopenia may lead to frailty, but
not all patients with sarcopenia are frail—sarcopenia is about
twice as common as frailty. Several studies have shown that
the risk of falls is significantly elevated in subjects with reduced
muscle strength. Treatment of sarcopenia remains
challenging, but promising results have been obtained using progressive
resistance
training, testosterone, estrogens, growth hormone, vitamin
D, and angiotensin-converting enzyme inhibitors. Interesting nutritional
interventions include high-caloric nutritional supplements
and essential amino acids that support muscle fiber synthesis.

Keywords Sarcopenia – Muscle mass – Prevalence – Morbidity

1 A history of muscle loss

The story of sarcopenia has a rather recent beginning, although a search of the terms muscle wasting and sarcopenia in the
online database PubMed buttresses its growing importance over the last years (Fig. 1).
Involutional changes of the musculature were described as early as 1931
by Macdonald Critchley, then junior neurologist
at King’s College Hospital in London, who wrote that
“the entire musculature tends with advancing age to undergo involutional
changes, which are manifested as wasting”[1].
He went on saying that “probably the chief cause of this change is to
be demonstrated in the general process of senile
atrophy, which shows itself in the muscles and
elsewhere.” Later on, in the 1970s, Nathan Shock published a series of
articles
on age-related physiologic functions using data from
the first large-scale longitudinal study in this field [2].
Altogether, it evolved that no decline in structure and function is
more dramatic than the decline in muscle mass that
develops as we age. Irwin Rosenberg realized that if
this phenomenon was to be taken seriously, a name was required, and at
a meeting in Albuquerque, New Mexico, in 1988, he
suggested to use the term sarcopenia [3]. Following the recommendation by Morley, the term took hold over these last 20 years. [4]

Fig. 1 Number of PubMed entries retrieved after entering the search term “muscle wasting OR sarcopenia”. Assessed on 23 October 2012
from www.pubmed.gov

2 How to measure muscle mass and muscle strength?

The name sarcopenia is derived from Greek sarx (flesh) and penia (loss), literally meaning poverty of flesh. Sarcopenia is one of the four main reasons for loss of muscle mass, the others
being anorexia, dehydration, and cachexia [5, 6]. It is difficult to estimate the prevalence of sarcopenia (Table 1),
mostly because of practical difficulties in assessing muscle mass. Many
different methodologies have been used over the
last 20 years, and new techniques are still being
introduced. On average, it is estimated that 5–13 % of elderly
people aged
60–70 years are affected by sarcopenia, and the
numbers increase to 11–50 % for those aged 80 or above [7].
In line with these data, other sources estimate that 8–40 % of
elderly people above the age of 60 years are affected by
sarcopenia [8]. Sarcopenia may lead to frailty, but not all patients with sarcopenia are frail. In essence, sarcopenia is about twice as
common as frailty [7].

The broadness in the range of sarcopenia
prevalence is partly due to the heterogenecity of study populations, but
also due
to the different techniques used to assess muscle mass.
Dual-energy X-ray absorptiometry (DEXA) is currently considered the
gold standard. The name is derived from the fact that two
X-ray beams are used with different energy levels of minimal intensity
[9]. Other methods used to measure muscle mass include bioelectrical impedance, computed tomography, magnetic resonance imaging,
urinary excretion of creatinine, anthropometric assessments, and neutron activation assessments [5]. Depending on the actual technique used in different studies and on the cutoff values chosen, the prevalence of muscle mass
may vary considerably (Table 1). Many institutions use handgrip strength as a standard measure for assessing muscle strength. Physical performance can be
analyzed using simple and easy-to-do tests such as the short physical performance battery test [10], usual gait speed [11], the timed get-up-and-go test [12], or the stair climb power test [13]. More recently, Scharf and Heineke have argued that “a combination of serum markers, diagnostic imaging, and functional
tests of muscle function would constitute an ideal biomarker panel” [14]. A recent consensus statement [15]
acknowledges that the list of potential serum markers of sarcopenia is
quite long. It embraces markers of inflammation (e.g.,
C-reactive protein, interleukin-6, and tumor necrosis
factor-), clinical parameters, urinary creatinine, hormones (e.g.,
dehydroepiandrosterone
sulfate, testosterone, insulin-like growth factor-1, and
vitamin D), products of oxidative damage, or antioxidants [15].
Since all the aforementioned markers are rather indirect measures of
muscle loss, novel serum markers directly associated
with changes in skeletal muscle mass and function are
also promising. The one mentioned in the consensus statement is
procollagen
type III N-terminal peptide (P3NP) [15]. Another interesting marker in this regard is C-terminal Agrin Fragment, a degeneration product of the neuromuscular junction
[16, 17].

3 Pathophysiological changes in sarcopenia

Using assessments of physical performance
it became clear that aging is associated with changes not only in muscle
mass but
also in muscle composition, contractile, and material
properties of muscle as well as in the function of tendons [18].
Therefore, recent consensus definitions include not only changes in
muscle mass, but also changes in muscle function like
exercise performance. In aging muscle, there is a loss of
motor units via denervation. These denervated motor units are recruited
by surviving motor units, which puts an increased burden
of work on them.

Altogether, there is a net conversion of fast type II muscle fibers into slow type I fibers with resulting loss in muscle
power necessary for activities of daily living such as rising from a chair or climbing steps.[18] Other aspects include the deposition of lipids within muscle fibers. These effects — in contrast to cachexia [6]
— do not lead to a net loss in body weight, but to a significant
reduction in muscle strength. Indeed, in healthy volunteers,
the maximal velocity during cycle ergometry decreased by
18 % from the third age decade (20–29 years) to the sixth
(50–59 years)
[19]. Another 20 % were lost between the seventh (60–69 years) and the ninth age decade (80–89 years) [19]. The loss of maximal oxygen consumption (peak VO2) with increasing age has also been attributed to reduced muscle mass and cardiac output [18].
Our group has recently demonstrated that 19.5 % of a prospectively
enrolled cohort of 200 patients with clinically stable
chronic heart failure fulfilled the criteria of
sarcopenia. Among these patients, muscle wasting remained an independent
predictor
of reduced peak VO2 after adjusting for age, gender, New York Heart Association class, hemoglobin value, left ventricular ejection fraction,
6-min walk distance, and the number of co-morbidities [20].
Importantly, the risk of falls and consequently of fractures in elderly
subjects is closely related to reduced muscle mass
as well: Another study found a 2.3-fold increase in the
risk of falls after multivariable adjustment among patients in the
lower third of handgrip strength as compared to the upper
third [21]. Likewise, another large-scale study in more than 2,100 elderly subjects found that a low walking speed is an independent
risk factor of falls [22].

4 Making a diagnosis of sarcopenia

Using the above knowledge, it does not
come as a surprise that the likelihood of having a physical disability
is higher in
elderly subjects who present with height-adjusted
appendicular muscle mass 2 standard deviations below the mean of young
adult
as compared to those with normal muscle mass [23].
Having said that, the difficulty in making a correct diagnosis of
sarcopenia is easily understood. Several definitions
and diagnostic criteria have been proposed over the last
20 years. Many of them are not easily applicable in daily clinical
practice.

A consensus definition formulated by experts from a vast array of different medical fields recently suggested to diagnose
sarcopenia when two criteria are fulfilled: (1) a low muscle mass and (2) a low gait speed [24]. Normal muscle mass is defined using data derived from young subjects aged 18–39 years from the Third NHANES population,
[25] and the requirement
for a diagnosis of sarcopenia is the presence of a muscle mass ≥2
standard deviations below the mean
of this reference population. This value can normally be
calculated automatically by equipment such as DEXA scanners. A low
gait speed is defined as a walking speed below
0.8 m/s in the 4-m walking test [26]. The European Working Group on Sarcopenia in Older People suggested diagnosing sarcopenia when at least two of three criteria
apply: (1) low muscle mass, (2) low muscle strength, and/or (3) low physical performance [27].
Cutoff points are defined in a similar manner as by the consensus group
mentioned before, namely 2 standard deviations
below the mean reference value for muscle mass and muscle
strength of a reference population and a gait speed ≤0.8 m/s. A
more recent consensus document [28]
defines “sarcopenia with limited mobility” as present in a person with
muscle loss whose walking speed is equal to or less
than 1 m/s or who walks less than 400 m during a
6-min walk, and who has a lean appendicular mass corrected for height
squared
of 2 standard deviations or more below the mean of
healthy persons between 20 and 30 years of age of the same ethnic
group.
However, these criteria remain cumbersome in daily
clinical practice, and easily applicable tests such as handgrip strength
testing or one of the biomarkers mentioned above may help
to identify patients in need of a more thorough examination.

No consensus has been reached so far as to whether the term sarcopenia should be limited to older persons above 60 years of
age or whether it should be used in adults of any age, particularly also in patients with chronic disease [28].

5 Treatment approaches to sarcopenia

A diagnosis of sarcopenia remains a rare
case. But even if the diagnosis is reached, the treatment of sarcopenia
remains challenging.
Many different approaches have been pursued, but exercise
and physical activity are important considerations for both sarcopenia
prophylaxis [29, 30] and sarcopenia management [31]. Progressive resistance training, performed two–three times per week by older people, has been shown to improve gait speed,
timed get-up-and-go, climbing stairs, and overall muscle strength [32]. Indeed, a recent study in patients with heart failure has shown that daily exercise using a cycle ergometer reduces the
expression of ligases from the ubiquitin-proteasome pathway [33].
Nutritional interventions also have an important impact. Current
recommendations state that protein should be consumed
at a rate of 0.8 g/kg/day, but about 40 % of
persons above the age of 70 years do meet this amount [34].
Additional calorie intake of 360 cal per day together with
resistance exercise training has been shown to increase leg
muscle strength in nursing home residents after
10 weeks. Similar effects were described in cachectic patients [35]. Supplementation of essential amino acids has been shown to improve handgrip strength and 6-min walking distance in elderly
subjects after 3 months [36].
Other therapeutic approaches include the use of testosterone,
estrogens, growth hormones, vitamin D, and angiotensin-converting
enzyme inhibitors [5, 30, 37].
In addition, animal studies have recently reported beneficial effects
of soluble activin receptor type IIB (ActRIIB) treatment
[38] and myostatin inhibition [39].

The first step in the sarcopenia journey
is to create more awareness of this clinical problem, both by the
general public
and by healthcare professionals. In this respect, the
implementation of standardized diagnostic criteria was extremely
important.
However, sarcopenia is a phenomenon that is present not
only in healthy elderly subjects but also in those with chronic
illnesses,
such as chronic heart or renal failure. More prospective
studies are required to understand the prevalence, incidence, phenotype,
and the clinical impact of sarcopenia. Such studies are
only beginning to emerge. Furthermore, the discussion continues whether
sarcopenia, i.e., loss of muscle mass, should be
separated from dynopenia, i.e., loss of power. Also, as enthusiasts try
to
make sarcopenia all encompassing by adding a functional
definition, the definition lines between frailty and sarcopenia are
becoming blurred. There is a need for a consensus
decision regarding the use of these terms.

Acknowledgments

This article is an updated and modified version of an article previously published by the same authors in the Journal of Cachexia, Sarcopenia and Muscle [40]. The authors of this manuscript certify that they comply with the ethical guidelines for authorship and publishing in the
Journal of Cachexia, Sarcopenia and Muscle (von Haehling S, et al. J Cachexia Sarcopenia Muscle 2010; 1:7–8.).

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